Peroxynitrite reaction products of 3',5'-di-O-acetyl-8-oxo-7, 8-dihydro-2'-deoxyguanosine.
Peroxynitrite reaction products of 3',5'-di-O-acetyl-8-oxo-7, 8-dihydro-2'-deoxyguanosine.
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3,5-二-O-乙酰基-8-氧代-7, 8-二氢-2-脱氧鸟苷的过氧亚硝酸盐反应产物。
DOI：
10.1073/pnas.96.21.11729
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发表时间：
1999
影响因子：
11.1
通讯作者：
Tannenbaum,SR
中科院分区：
文献类型：
--
作者：
Niles,JC;Burney,S;Singh,SP;Wishnok,JS;Tannenbaum,SR
在DNA碱基中，过氧亚硝酸根（ONOO−）对2′-脱氧鸟苷（dGuo）的反应性最强，但对8-氧代-7，8-二氢-2 ′-脱氧鸟苷（8-oxodGuo）的反应性更强，需要1，000倍过量的dGuo才能提供50%的保护。因此，8-oxodGuo是DNA中潜在的重要靶点，并且应该表征与ONOO−的反应产物的结构，这似乎是合理的。以3′，5 ′-di-O-Ac-8-oxodGuo为模型化合物，在模拟生理反应条件（pH 7.2的磷酸盐/碳酸氢盐缓冲液）下，分离并鉴定了与ONOO−的反应产物。主要反应产物II不稳定，经碱介导水解生成2，5-二氨基咪唑-4-酮IIa和3-（3，5-二-O-Ac-2-脱氧-β-d-吡喃-戊呋喃糖基）-5-亚氨基咪唑烷-2，4-二酮IIb。后一种化合物进一步水解为3-（3，5-二-O-Ac-2-脱氧-β-d-吡喃-戊呋喃糖基）异戊尿酸，IIc。其它产物包括3-（3，5-二-O-Ac-2-脱氧-β-d-邻位-戊呋喃糖基）-2，4，6-三氧代-[1，3，5]三嗪烷-1-甲脒，I，其进一步水解为1-（3，5-二-O-Ac-2-脱氧-β-d-邻位-戊呋喃糖基）氰尿酸，Ia。1-（3，5-二-O-Ac-2-脱氧-β-d-邻-呋喃戊糖基）对羟基苯甲酸（III）是一种次要产物，也可能有助于形成IIc。在这些反应中形成的主要产物是生物学上未表征的，但类似于已被证明是预诱变和DNA聚合的阻滞剂的修饰的DNA碱基。
Of the DNA bases, peroxynitrite (ONOO−) is most reactive toward 2′-deoxyguanosine (dGuo), but even more reactive with 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodGuo), requiring a 1,000-fold excess of dGuo to provide 50% protection against the reaction with 8-oxodGuo. Therefore, it seems reasonable that 8-oxodGuo is a potentially important target in DNA and that the structures of the reaction products with ONOO−should be characterized. Using 3′,5′-di-O-Ac-8-oxodGuo as a model compound, the reaction products with ONOO−have been isolated and identified under simulated physiological reaction conditions (phosphate/bicarbonate buffer at pH 7.2). The major reaction product, II, is unstable and undergoes base-mediated hydrolysis to 2,5-diaminoimidazol-4-one, IIa, and 3-(3,5-di-O-Ac-2-deoxy-β-d-erythro-pentofuranosyl)-5-iminoimidazolidine-2,4-dione, IIb. The latter compound further hydrolyzes to 3-(3,5-di-O-Ac-2-deoxy-β-d-erythro-pentofuranosyl)oxaluric acid, IIc. Other products include 3-(3,5-di-O-Ac-2-deoxy-β-d-erythro-pentofuranosyl)-2,4,6-trioxo-[1,3,5]triazinane-1-carboxamidine, I, which further hydrolyzes to 1-(3,5-di-O-Ac-2-deoxy-β-d-erythro-pentofuranosyl)cyanuric acid, Ia. 1-(3,5-di-O-Ac-2-deoxy-β-d-erythro-pentofuranosyl)parabanic acid, III, is a minor product that also may contribute to formation of IIc. The major products formed in these reactions are biologically uncharacterized but are similar to modified DNA bases that have been shown to be both premutagenic and blocks to DNA polymerization.